Project Summary Mortality from infectious diseases remains a leading cause of death worldwide, making the development of new vaccines an important priority of biomedical research. Immunologic memory is a cardinal feature of adaptive immunity and an important goal of vaccination strategies. Traditional vaccination strategies are very effective at generating neutralizing antibodies against bacteria and viruses. However, a vaccine capable of generating robust T lymphocyte memory is still beyond our research, due, in part, to an incomplete understanding of how lymphocyte fates are specified. In this grant application, we propose to study the role of proteasome degradation activity in controlling this process.